RESUMEN
BACKGROUND: This study, for the first time, compared illness and antidepressant response characteristics of young subjects with major depression (MDD) at low (LRMDD) or high-risk (HRMDD) for developing bipolar disorder with characteristics of young bipolar (BPD) subjects and healthy controls (HC). METHODS: One hundred and six young (15-30â¯yr), medication-free subjects MDD subjects (HRMDD, Nâ¯=â¯51; LRMDD, Nâ¯=â¯55) were compared with 32 BPD (Type I: 14; Type II: 18) as well as 49 HC subjects. Baseline illness characteristics and frequency of comorbid conditions were examined using Analysis of Variance and Cochran-Armitage trend test. Additionally, in MDD subjects, the effect of open-label antidepressant treatment for up to 24 months with periodic assessments was compared between HRMDD and LRMDD groups for treatment response, remission and (hypo)mania switch while controlling for attrition. RESULTS: Significant gradation from LRMDD to HRMDD to BPD groups was found for increasing occurrence of alcohol dependence (pâ¯=â¯0.006), comorbid PTSD (pâ¯=â¯0.006), borderline personality traits (pâ¯=â¯0.001), and occurrence of melancholic features (pâ¯<â¯0.005). Antidepressant treatment response was similar between the two groups except that for the 12-month period HRMDD showed a trend for a lower response. Switch to (hypo)mania was infrequent in both groups though the HRMDD showed a higher occurrence of spikes in (hypo)mania symptoms (>25% increase in YMRS scores)(pâ¯=â¯0.04). CONCLUSION: Findings of the study indicate that a substantial proportion of young MDD subjects share BPD illness characteristics. These HRMDD subjects, if treated with antidepressants, need to be monitored for development of BPD. TRIAL REGISTRATION: NCT01811147.
Asunto(s)
Antidepresivos/farmacología , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/fisiopatología , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/fisiopatología , Progresión de la Enfermedad , Evaluación de Resultado en la Atención de Salud , Adolescente , Adulto , Alcoholismo/epidemiología , Trastorno Bipolar/epidemiología , Trastorno de Personalidad Limítrofe/epidemiología , Comorbilidad , Trastorno Depresivo/epidemiología , Trastorno Depresivo Mayor/epidemiología , Femenino , Humanos , Estudios Longitudinales , Masculino , Riesgo , Adulto JovenRESUMEN
The neurobiology and neurochemistry of bipolar disorder and its different phases are poorly understood. This study investigated metabolite abnormalities in both unmedicated bipolar depression as well as mania using 2D 1H magnetic resonance spectroscopy imaging (MRSI). MRSI data were obtained from 24 unmedicated bipolar disorder (BP) subjects (12 (hypo)manic (BPM)) and 12 depressed (BPD), and 20 closely matched healthy controls. 2D 1H MRSI data were collected from a 15-mm axial slice placed along the anterior commissure-posterior commissure (AC-PC) line to measure brain metabolites bilaterally in the thalamus and also the anterior and posterior cingulate cortex (ACC and PCC). Brain Lac/Cr levels were significantly increased in the BP group as a whole compared to healthy controls. Glutamate abnormalities varied across bipolar state as well as brain region: significantly increased Glx/Cr values were found in the left thalamus in BPD, but BPM had decreased Glu/Cr and Glx/Cr levels in the PCC when compared to healthy controls and decreased Glu/Cr levels even when compared to the BPD subjects group. The findings of the study point to state-related abnormalities of oxidative and glutamate metabolism in bipolar disorder.
Asunto(s)
Trastorno Bipolar/patología , Encéfalo/metabolismo , Creatina/metabolismo , Ácido Láctico/metabolismo , Espectroscopía de Resonancia Magnética , Adulto , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Encéfalo/patología , Femenino , Ácido Glutámico/metabolismo , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Tritio , Adulto JovenRESUMEN
BACKGROUND: Impaired response inhibition and poor impulse control are hallmarks of the manic phase of bipolar disorder but are also present during depressive and, to a lesser degree, euthymic periods. The neural mechanisms underlying these impairments are poorly understood, including how mechanisms are related to bipolar trait or state effects. METHODS: One-hundred four unmedicated participants with bipolar mania (BM) (n = 30), bipolar depression (BD) (n = 30), bipolar euthymia (BE) (n = 14), and healthy control subjects (n = 30) underwent functional magnetic resonance imaging during emotional and nonemotional go/no-go tasks. The go/no-go task requires participants to press a button for go stimuli, while inhibiting the response to no-go trials. In separate blocks, participants inhibited the response to happy faces, sad faces, or letters. RESULTS: The BE group had higher insula activity during happy face inhibition and greater activity in left inferior frontal gyrus during sad face inhibition, demonstrating bipolar trait effects. Relative to the BE group, BD and BM groups demonstrated lower insula activity during inhibition of happy faces, though the depressed sample had lower activity than manic patients. The BD and BM groups had a greater response to inhibiting sad faces in emotion processing and regulation regions, including putamen, insula, and lateral prefrontal cortex. The manic group also had higher activity in insula and putamen during neutral letter inhibition. CONCLUSIONS: These results suggest distinct trait- and state-related neural abnormalities during response inhibition in bipolar disorder, with implications for future research and treatment.
Asunto(s)
Trastorno Bipolar/fisiopatología , Encéfalo/fisiopatología , Emociones/fisiología , Neuroimagen Funcional/psicología , Inhibición Psicológica , Imagen por Resonancia Magnética/psicología , Adolescente , Adulto , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/psicología , Estudios de Casos y Controles , Expresión Facial , Neuroimagen Funcional/métodos , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Estimulación Luminosa/métodos , Desempeño Psicomotor/fisiología , Percepción Visual/fisiologíaRESUMEN
BACKGROUND: Recent studies indicate that modulation of glutamate neurotransmission is associated with antidepressant response. Lamotrigine, an anticonvulsant which decreases presynaptic glutamate release, has been shown to be effective in the depressive phase of bipolar disorder (BD-D); however, only 40-50% of patients have a full response. This pilot study investigated whether memantine, a low-affinity N-methyl-D-aspartate (NMDA) receptor antagonist approved for Alzheimer's disease, can augment the effects of lamotrigine. METHODS: BD-D outpatients in a major depressive episode on a stable dose of lamotrigine (100 mg or more) were randomized to either memantine (starting dose of 5 mg increased up to 20 mg over four weeks, then 20 mg stable dose from four to eight weeks) or matching pill placebo for eight weeks. Patients were rated on the 17-item Hamilton Depression Rating Scale (HDRS) and other behavioral measures weekly. RESULTS: The eight-week repeated-measures mixed-effect model for HDRS was not significant for memantine (n = 14) versus placebo (n = 15). Exploratory mixed-effect analyses for the first four weeks, while the memantine dose was being titrated up every week, revealed a significant decrease in HDRS scores from baseline (p = 0.007). CONCLUSION: This proof-of-concept study failed to show a statistically significant benefit of memantine augmentation of lamotrigine for patients with BD-D over eight weeks. However, memantine had an antidepressant effect early on in the treatment while its dose was being titrated up. Larger placebo-controlled studies are needed to ascertain optimal timing and dosing for memantine augmentation of lamotrigine in BD-D.